September 11, 2012

Nonconscious Mind Plays Significant Role In Placebo Response

The unconscious mind plays a key role in the placebo effect, researchers have found, allowing them to identify a novel mechanism that helps explain the power of placebos and nocebos.

The new finding demonstrates that the placebo effect can be activated outside of conscious awareness, and provide an explanation for how patients can show clinical improvement even when they receive treatments devoid of active ingredients or of known therapeutic efficacy. The study was published online in the Proceedings of the National Academy of Sciences (PNAS).

"In this study, we used a novel experimental design and found that placebo and nocebo [negative placebo] effects rely on brain mechanisms that are not dependent on cognitive awareness," explains Karin Jensen, PhD, of the Department of Psychiatry and the Martinos Center for Biomedical Imaging at Massachusetts General Hospital (MGH) and the Program in Placebo Studies (PiPS) at Beth Israel Deaconess Medical Center/Harvard Medical School. "A person can have a placebo or nocebo response even if he or she is unaware of any suggestion of improvement or anticipation of getting worse."

Scientists have long believed that the placebo effect was related to conscious beliefs or thoughts, and that when given an inert pill or therapy, patients get better because they have the expectation that they will get better. Or in the case of nocebos, they get worse because they anticipate that they will get worse.

Recently, though, scientists have recognized that people's expectation of reward or threat is learned quickly and automatically without needing to consciously register the idea in their brains. Neuroimaging studies of the human brain have suggested that certain structures, such as the striatum and the amygdala, can process incoming stimuli before they reach conscious awareness, and, as a result, may mediate non-conscious effects on human cognition and behavior.

The scientists set out to determine whether placebo and nocebo responses might be activated outside of a person's conscious awareness, even if he or she has no expectation of either improving or declining.

Most of us know that a placebo is an inert treatment that makes the patient or test subject feel better through the power of suggestion. A nocebo works the same way, suggestion and conditioning, but it creates negative effects.

According to the Harvard Medical School's Health Publications, "A placebo makes patients feel better for reasons unrelated to the specific healing properties of the treatment. A nocebo makes patients feel worse (or does other harm) in the same way. Common symptoms are drowsiness, headache, mild dizziness, difficulty concentrating, and stomach upset." An example of a nocebo is a study where volunteers were told that a mild electrical current would be passed through their heads and it might cause a headache. No current was actually passed, but two-thirds of the participants developed headaches.

The research team, including scientists from Plymouth University and the Karolinska Institute, studied 40 healthy volunteers (24 female; 16 male, median age 23). Two experiments were conducted: In the first, researchers administered heat stimulation to participants' arms while simultaneously showing them images of male human faces on a computer screen. The heat stimulation stayed the same throughout, but the faces shown displayed two responses: one associated with low pain stimulations and one with high pain.

Participants were then asked to rate their pain experience on a scale of 0 to 100, with 0 being no pain and 100 being the worst pain imaginable. As predicted, the pain ratings correlated with the previously learned associations, with a pain rating of 19 when the subjects saw the low pain face while the high pain face resulted in subjects' mean reports of 53 on the pain scale (nocebo effect).

In the second experiment, the participants were given the same level of heat stimulation while the same faces were flashed on a screen too quickly for conscious recognition. The participants again rated their pain, and despite a lack of consciously recognizable cues, the participants reported a mean pain rating of 25 in response to the low pain face (placebo effect) and a mean pain rating of 44 in response to the high pain face (nocebo response) even though they did not consciously recognize the faces on the screen.

"Such a mechanism would generally be expected to be more automatic and fundamental to our behavior compared to deliberate judgments and expectations," explains Jian Kong of MGH and the PiPS. "Most important, this study provides a unique model that allows us to further investigate placebo and nocebo mechanisms by using tools such as neuroimaging."

As PiPS Director Ted Kaptchuk notes, "It's not what patients think will happen [that influences outcomes] it's what the nonconscious mind anticipates despite any conscious thoughts. This mechanism is automatic, fast and powerful, and does not depend on deliberation and judgment. These findings open an entirely new door towards understanding placebos and the ritual of medicine."